Synthesis and kinetics of oxidation of some dipeptides with anodically generated manganese(III) sulphate: Mechanistic study

Dipeptides (DP) namely phenylalanyl–proline (Phe–Pro), isoleucyl–proline (Ile–Pro), and leucyl–proline (Leu–Pro) were synthesized by classical solution method and characterized. The kinetics of oxidation of these DP by Mn(III) have been studied in the presence of sulphate ions in acidic medium at 26°C. The reaction was followed spectrophotometrically at λ_max = 500 nm. A first‐order dependence of rate on both [Mn(III)]₀ and [DP]₀ was observed. The rate is independent of the concentration of reduction product, Mn(II), and hydrogen ions. The effects of varying dielectric constant of the medium and addition of anions such as sulphate, chloride, and perchlorate were studied. The activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of DP with Mn(III) in the rate‐limiting step is suggested. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 438–444, 2002     

Mn(III) oxidation of peptides: A mechanistic investigation of kinetic variations in hydrophobic‐induced oxidation of tetrapeptides of elastin sequences

Four tetrapeptide analogues of elastin sequences, glycyl‐glycyl‐alanyl‐proline (GGAP), glycyl‐glycyl‐valyl‐proline (GGVP), glycyl‐glycyl‐isoleucyl‐proline (GGIP), and glycyl‐glycyl‐phenylalanyl‐proline (GGFP) were synthesized, based on their increasing order of hydrophobicity, by a classical solution phase method and were characterized. These tetrapeptides (TETPs) were oxidized using Mn(OAc)₃ in 25% acetic acid at 298 K, and the kinetics of the reaction was monitored spectrophotometrically at λ_max = 400 nm. A first‐order dependence of rate on each of [Mn(OAc)₃], [OAc^?], and substrate [TETP], an inverse order dependence on [H⁺], has been observed. The rate is independent of [Mn(II)]. However, an inverse order dependence on varying the dielectric constant using various percentages (v/v) of acetic acid has also been observed, and but addition of anions such as Cl^? and ClO₄^? has insignificant effect on the rate. Activation parameters have been evaluated using the Arrhenius and Erying plots. The oxidation products were isolated and characterized. Based on the results obtained, a plausible mechanism involving [Mn(OAc)₄]^? has been proposed. An apparent correlation was noted between the rate of oxidation of these TETPs by Mn(III) in the presence of sulfate ions in sulfuric acid medium and Mn(OAc)₃ in the acetic acid medium. The rate of oxidation with Mn(OAc)₃ was observed to be slower than with the former. The rate of oxidation of GGFP was found to be higher than GGIP, GGVP, and GGAP. This may be due to the presence of an aromatic side chain and/or because of the increased hydrophobicity. The overall order of rate of oxidation of TETPs is GGFP > GGIP > GGVP > GGAP, which also represents an increasing order of their hydrophobicity. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 38: 115–123, 2006     

Effect of cationic micellar aggregates on the kinetics of oxidation of aminoalcohols by N-bromosuccinimide in alkaline medium

The kinetics of oxidation of some aminoalcohols (AA), viz. ethanolamine, diethanolamine, and triethanolamine, by N-bromosuccinimide (NBS) in alkaline medium has been investigated in the absence as well as in the presence of cetyltrimethylammonium bromide (CTAB), a cationic surfactant. The reaction always followed a first-order dependence of rate on NBS, while the order in each AA and alkali was found to decrease from unity to zero at higher [AA] and [OH-], respectively. The reaction is strongly catalyzed by CTAB even before the critical micelle concentration (CMC) of CTAB. However, the observed rate constants attained constancy at higher [CTAB] (>CMC of CTAB). The premicellar kinetics has been rationalized in the light of the Piszkiewicz positive cooperativity model [J. Am. Chem. Soc. 99 (1977) 1550]. The binding constants between the reactants and the surfactant have also been evaluated using the Raghvan and Srinivasan model [Proc. Ind. Acad. Sci. 98 (1987) 199], which is applicable to bimolecular micellar catalyzed reaction and predicts constancy in the observed rate constant at higher [surfactant]. The binding constants obtained by both the models are in good agreement.     

Hydrophobicity dependence of oxidation of tetrapeptides of elastin sequences with Mn(III): Synthesis,characterization, kinetics,and mechanistic study

The analogues of elastin sequences, glycyl‐glycyl‐alanyl‐proline (GGAP), glycyl‐glycyl‐phenylalanyl‐proline (GGFP), and glycyl‐glycyl‐isoleucyl‐proline (GGIP) were synthesized by classical solution phase method and characterized. The kinetics of oxidation of these tetrapeptides (TETP) by Mn(III) has been studied in the presence of sulphate ions in acidic solution at 25°C. The reaction was followed spectrophotometrically at λ_max = 500 nm. A first‐order dependence of rate on both [Mn(III)] and [TETP] was observed. The rate is independent of the concentration of the reduction product, Mn(II), and hydrogen ions. The effects of varying the dielectric constant of the medium and addition of anions such as sulphate, chloride, or perchlorate were studied. Activation parameters have been evaluated using Arrhenius and Erying plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of TETP with Mn(III) in the rate‐limiting step is suggested. An apparent correlation was noted between the rate of oxidation and the hydrophobicity of these sequences, where increased hydrophobicity results in increased rate of oxidation. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 34: 39–48, 2002     

Thermosensitive gel formation of novel polypeptides containing a collagen‐derived Pro‐Hyp‐Gly sequence and an elastin‐derived Val‐Pro‐Gly‐Val‐Gly sequence

A triple‐helix‐forming collagen model peptide, (prolyl‐trans‐4‐hydroxyprolyl‐glycyl)₁₀ [(Pro‐Hyp‐Gly)₁₀], and a thermosensitive elastin‐derived pentapeptide, valyl‐prolyl‐glycyl‐valyl‐glycyl (Val‐Pro‐Gly‐Val‐Gly), were copolymerized in various mole ratios using 1‐ethyl‐3‐(3‐dimethylaminopropyl)‐carbodiimide hydrochloride and 1‐hydroxybenzotriazole in dimethyl sulfoxide at 20 °C. All of the obtained polypeptides have molecular weight higher than 10³ and contain a triple‐helical structure, and showed an inverse phase transition from transparent solution to turbid suspension in response to a rise in temperature. The lower critical solution temperature of the polypeptide solution decreased upon increasing the content of Val‐Pro‐Gly‐Val‐Gly. Furthermore, polypeptides containing 82–86 mol % of Val‐Pro‐Gly‐Val‐Gly in composition showed reversible gel formation, suggesting that (Pro‐Hyp‐Gly)₁₀ acts as a hydrated unit and Val‐Pro‐Gly‐Val‐Gly acts as a thermosensitive crosslinking point. These biodegradable thermosensitive polypeptides may be useful for biomedical applications, including, as a scaffold for tissue regeneration. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6048–6056, 2005     

Kinetics and mechanism of oxidation of aspirin by bromamine-T,N-bromosuccinimide,and N-bromophthalimide

The kinetics of the oxidation of aspirin (ASP) by bromamine-T (BAT), N-bromosuccinimide (NBS), and N-bromophthalimide (NBP) has been studied in aqueous perchloric acid at 303 K. The oxidation reaction follows identical kinetics with first-order in [oxidant], fractional-order in [ASP], and inverse fractional-order in [H⁺]. Under identical experimental conditions the extent of oxidation with different oxidizing agents is in the order: NBS>BAT>NBP. The rate decreased with decreasing dielectric constant of the medium. The variation of ionic strength and the addition of the reaction products and halide ions had no significant effect on the reaction rate. The solvent isotope effect was studied using D₂O. Kinetic parameters were evaluated by studying the reaction at different temperatures. The reaction products were identified by GC–MS. The proposed reaction mechanism and the derived rate law are consistent with the observed kinetic data. Formation and decomposition constants for ASP-oxidant complexes have been evaluated. Decarboxylation, bromination, and loss of acetic acid gave 2,4,6-tribromophenol. © 1998 John Wiley & Sons, Inc. Int J Chem Kinet: 30: 407–414, 1998     

Anodically generated manganese(III) sulphate for the oxidation of dipeptides in aqueous sulphuric acid medium: A kinetic study

The kinetic of oxidation of dipeptides (DP) namely valyl-glycine (Val-Gly), alanyl-glycine (Ala-Gly) and glycyl-glycine (Gly-Gly), by Mn(III) have been studied in the presence of sulphate ions in acid medium at 26°C. The reaction was followed spectrophotometrically at λ_max = 500 nm. A first-order dependence of the rate on both [Mn(III)]_o and [DP]_o was observed. The rate is independent of the concentration of reduction product, Mn(II) and hydrogen ions. The effects of varying the dielectric constant of the medium and addition of anions such as sulphate, chloride and perchlorate were studied. The activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of DP with Mn(III) in the rate-limiting step is suggested. An apparent correlation was noted between the rate of oxidation and the hydrophobicity of these dimers, where increased hyphobicity results in increased rate of oxidation     

Oxidation of L‐amino acids by metal ion (Mn3+) in sulfuric acid medium: Effect of nucleophilicity and hydrophobicity on reaction rate

The kinetics of oxidation of L ‐amino acids (AAs) glycine( 1a ), alanine( 1b ), valine( 1c ), isoleucine( 1d ), leucine( 1e ), proline( 1f ), and phenylalanine( 1g ) by a transition metal ion (Mn³⁺) was studied in the presence of sulfuric acid medium at 26°C by a spectrophotometrical (λ_max = 500 nm) method. In all cases, the kinetics of reactions was of first‐order with respect to each [AA] and [Mn³⁺]. Increased [H⁺], [Mn²⁺] (the reduction product of Mn³⁺), sulfate, and chloride had no effect on the reaction rate. However, the reaction rate increased with increased dielectric constant of the medium. Oxidation rate increased for 1a–g and an apparent correlation was observed between the rate of oxidation and nucleophilicty of AAs except for 1a and 1g . The reaction rate also linearly depended on the hydrophobicity of AAs except for 1f and 1g . The thermodynamic parameters for AA‐metal ion complex formation and activation parameters for the rate‐limiting steps have been evaluated. Analysis of the oxidation products indicated that the AAs underwent oxidative deamination and decarboxylation to form corresponding aldehydes. Based on these data, plausible mechanisms involved in the oxidation of AAs are proposed. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 599–607, 2011     

Kinetics and mechanism of oxidation of diethyl ketone by N-bromosuccinimide

Oxidative kinetics of diethyl ketone in perchloric acid media in the presence of mercuric acetate have been studied by using N-bromosuccinimide (NBS) as oxidant in the temperature range of 25°-50°C. It has been found that the order with respect to NBS is zero while with respect to diethyl ketone and [H⁺], it is unity. Succinimide, sodium perchlorate, and mercuric acetate have an insignificant effect on the reaction rate, while the dielectric effect was negative. A solvent isotope effect (k0_D2O/k0_H2O = 1.6–1.8) at 35°C has been observed. On the basis of the available evidences a suitable mechanism consistent with the experimental results has been proposed in which it is suggested that the mechanistic route for NBS oxidation in an acidic medium is through the enol form of the ketone. The magnitude of the solvent effect also supports the mechanism. Various activation parameters have been calculated, and the 1,2-dicarbonyl compound has been identified as the end product of the reaction.     

Oxidation of 2‐Phenylethylamine with N‐Bromosuccinimide in Acid and Alkaline Media: A Kinetic and Mechanistic Study

A kinetic study of oxidation of 2‐phenylethylamine (PEA), a bioactive compound, with potent oxidant, N‐bromosuccinimide (NBS) has been carried out in HCl and NaOH media at 313 K. The experimental rate laws obtained are: ‐d [NBS] /dt = k[NBS][PEA][H⁺] in hydrochloric acid medium and ‐d [NBS]/dt = k[NBS][PEA]^x[OH^?]^y in alkaline medium where x and y are less than unity. Accelerating effect of [Cl^?], and retardation of the added succinimide on the reaction rate have been observed in acid medium. Variation of ionic strength of the medium shows negligible effect on rate of reaction in both media. Decrease in dielectric permittivity of the medium decreased the rate in both media. The stoichiometry of the reaction was found to be 1:1 in acid medium and 1:2 in the case of alkaline medium. The oxidation products of PEA were identified as the corresponding aldehyde and nitrile in acid and alkaline medium, respectively. The reactions were studied at different temperatures and the activation parameters have been evaluated. The reaction constants involved in the proposed mechanisms were computed. The reaction was found to be faster in alkaline medium in comparison with the acid medium, which is attributed to the involvement of different oxidizing species. The proposed mechanisms and the derived rate laws are consistent with the observed experimental results.     

Mechanistic Investigations of Oxidation of Some Dipeptides by Sodium N‐chloro‐p‐toluenesulfonamide in Alkaline Medium:A Kinetic Study

The kinetics of oxidation of five dipeptides (DPP) viz., glycylglycine (Gly-Gly), L-alanyl-L-alanine (Ala-Ala), L-valyl-L-valine (Val-Val), L-leucyl-L-leucine (Leu-Leu) and phenylglycyl-phenylglycine (Phg-Phg) by sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in NaOH medium was studied at 308 K. The reactions follow identical kinetics for all the dipeptides, being first-order dependence each on [CAT]_o, [DPP]_o and fractional-order on [OH^－]. Addition of p-toluenesulfonamide or halide ions (Cl^－ or Br^－) has no significant effect on the rate of reaction. The reaction rate was found to increase with increase in ionic strength of the medium. The solvent isotope effect was studied using D₂O. The activation parameters for the reaction were computed from Arrhenius plots. Equilibrium and decomposition constants were evaluated. The oxidation products of the dipeptides were identified as their corresponding aldehydes. An isokinetic relationship was observed with β＝352 K, indicating that enthalpy factors control the reaction rate. CH₃C₆H₄SO₂NCl^－ of the oxidant has been postulated as the reactive oxidizing species. Under comparable experimental conditions, the rate of oxidation of the dipeptides increases in the order: Phg-Phg＞Ala-Ala＞Val-Val＞Leu-Leu＞Gly-Gly. The kinetics of oxidation of the dipeptides have also been compared with those of their corresponding monomer amino acids. The observed results have been explained by a plausible mechanism and the related rate law has been deduced.     

Mechanistic investigation of oxidation of metronidazole and tinidazole with N-bromosuccinimide in acid medium: A kinetic approach

Metronidazole (MTZ) and tinidazole (TNZ) belong to nitroimidazole group of drugs used to treat infections such as ameobiasis, giardiasis and trichomoniasis. The kinetics of oxidation of MTZ and TNZ with _N-bromosuccinimide (NBS) in perchloric acid medium has been investigated at 308 K. A 1:1 stoichiometry has been observed in both MTZ and TNZ cases. The oxidation reactions of both MTZ and TNZ follow the same rate law, -d[NBS]/dt = [NBS][Sub][H⁺]. However, in case of MTZ, at higher concentrations of H⁺ (0.006–0.01 mol dm^?3), the rate law obtained is -d[NBS]/dt = [NBS][MTZ][H⁺]^?1. Accelerating effect of [Cl^-] and retardation of the added succinimide on the reaction rate have been observed in the case of MTZ. The reactions were examined with reference to changes in concentration of added neutral salt, ionic strength and dielectric permittivity of the medium. The overall activation parameters have been evaluated from the Arrhenius plot. The reactive oxidizing species of NBS have been determined. The main oxidation products were identified by IR and ¹H NMR spectral analyses. The observed results have been explained by plausible mechanisms and the relative rate laws have been deduced.     

Cu(II) promoted oxidation of L-valine by hexacyanoferrate(III) in cationic micellar medium

The kinetics of Cu(II) accelerated L-valine (Val) oxidation by hexacyanoferrate(III) in CTAB micellar medium were investigated by measuring the decline in absorbance at 420 nm. By adjusting one variable at a time, the progression of the reaction has been inspected as a function of [OH⁻], ionic strength, [CTAB], [Cu(II)], [Val], [Fe(CN)₆³⁻], and temperature using the pseudo-first-order condition. The results show that [CTAB] is the critical parameter with a discernible influence on reaction rate. [Fe(CN)₆]^3- interacts with Val in a 2:1 ratio, and this reaction exhibits first-order dependency with regard to [Fe(CN)₆³⁻]. In the investigated concentration ranges of Cu(II), [OH⁻], and [Val], the reaction demonstrates fractional-first-order kinetics. The linear increase in reaction rate with added electrolyte is indicative of a positive salt effect. CTAB significantly catalyzes the process, and once at a maximum, the rate remains almost constant as [CTAB] increases. Reduced repulsion between surfactant molecules' positive charge heads brought on by the negatively charged [Fe(CN)₆]^3-, OH⁻, and [Cu(OH)₄]^2- molecules may be responsible for the observed drop in CMC of CTAB.     

Kinetics and mechanism of oxidation of ferrocyanide by N-bromosuccinimide in aqueous acidic solution

The kinetics of oxidation of ferrocyanide by N-bromosuccinimide (NBS) has been studied spectrophotometrically in aqueous acidic medium over temperature range 20–35 °C, pH = 2.8–4.3, and ionic strength = 0.10–0.50 mol dm⁻³ over a range of [Fe²⁺] and [NBS]. The reaction exhibited first order dependence on both reactants and increased with increasing pH, [NBS], and [Fe²⁺]. The rate of oxidation obeys the rate law: d[Fe³⁺]/dt = [Fe(CN)₆]^4–[HNBS⁺]/(k ₂ + k ₃/[H⁺]). An outer-sphere mechanism has been proposed for the oxidation pathway of both protonated and deprotonated ferrocyanide species. Addition of both succinimide and mercuric acetate to the reaction mixture has no effect on the reaction rate under the experimental conditions. Mercuric acetate was added to the reaction mixture to act as scavenger for any bromide formed to ensure that the oxidation is entirely due to NBS oxidation.     

Kinetics and mechanism of the oxidation of diaqua(nitrilotri- acetato)chromium(III) complex by N-bromosuccinimide

The kinetics of oxidation of the diaqua(nitrilotriacetato)chromium(III) complex [CrIIInta(H2O)2], by N-bromosuccinimide (NBS) to chromium(VI) in aqueous solution obeys the equation: where k1 is the rate constant for the electron-transfer process, K1 the equilibrium constant for the dissociation of [CrIIInta(H2O)2] to [CrIIInta(H2O)(OH)]−, and K2 is the pre-equilibrium formation constant for the precursor complex [CrIIInta(OH)(NBS)]−. The thermodynamic activation parameters were calculated and it is proposed that electron transfer proceeds via an inner-sphere mechanism. This revised version was published online in June 2006 with corrections to the Cover Date.     

Electron transfer reactions of V(IV) with Cl(I), Br(I) and I(I). A kinetic study

A kinetic study on the oxidation of V(IV) by chloramine-T (CAT) at pH 6.85 by N-bromo succinimide (NBS) in aqueous acetic acid–perchloric acid media and by N-iodo succinimide (NIS) in aqueous perchloric acid medium has been carried out. In all the systems studied the order with respect to the oxidant is unity. NBS and CAT oxidation reactions exhibited Michaelis–Menten type kinetics, and the NIS study indicated unit dependence on [substrate]. Independence on acidity has been observed in the case of CAT and NBS reactions, but NIS reactions exhibited inverse unit dependence on [acid]. Novel solvent influences have been noticed in the case of CAT reactions, but with NIS and NBS reactions retardation in the rate has been observed with an increase in the percentage of acetic acid. Plausible mechanisms consistent with the results have been postulated, and suitable rate laws in consonance with the postulated mechanisms have been derived.     

LC Separation and Online MS Characterization of Saturated and Unsaturated Alginic Acid Oligomers

We report the complete separation and characterization by online high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) of fully saturated alginic acid (AA) oligosaccharides from DP1 to beyond DP23, obtained by a chemical process, and unsaturated oligomers from DP1 to DP10, produced by lyase treatment. A series of negatively charged species of different m/z ratio are seen for each oligosaccharide. Smaller AA species, from DP1 to DP4, mainly furnish [M–H]^? anions whereas the DP5 to DP9-10 oligomers predominantly exist as the 2- charge state. The AA oligomers from DP10 to DP17 are mainly represented by the [M–3H]^3? anions whereas species from DP18 to DP23 are characterized by the 4? charge state. Online LC-ESI-MS enabled separation and simultaneous characterization of complex saturated and unsaturated AA oligomer mixtures without previous sample treatment, in particular extensive removal of salts to obtain species compatible with ESI-MS.     

Kinetics and mechanism of Ru(III) catalysed oxidation of some polyhydric alcohols by N-bromosuccinimide in acidic media

Kinetics of oxidation of ethylene glycol, glycerol, erythritol and dulcitol by acidic solution of N-bromosuccinimide (NBS) in presence of ruthenium(III) chloride as a homogeneous catalyst and mercuric acetate as scavenger in the temperature range of 30–50°C have been reported. The reactions follow identical kinetics, being first order in each NBS, substate and Ru(III). Zero effect of [H⁺], [mercuric acetate] and ionic strength has been observed. A negative effect of succinimide and acetic acid is observed while [Cl^-] shows the positive effect on reaction velocity. Various activation parameters have been computed. The products of the reaction were identified as the coresponding acids. A suitable mechanism consistent with the experimental results has been proposed.     

Inner-sphere oxidation of 2-aminomethylpyridinecobalt(II) complex by N-bromosuccinimide

The kinetics of the oxidation of the 2-aminomethylpyridineCo^II complex by N-bromosuccinimide (NBS), have been studied in aqueous solutions under various conditions, and obey the following rate law:Rate = [NBS][Co(L)(H₂O)₂]²⁺[k₂₊k₃/[H⁺]]An inner-sphere mechanism is proposed for the oxidation pathway for both protonated and deprotonated complex species, with the formation of an intermediate, which is slowly converted into the final oxidation products. The reaction rate is increased by increasing the pH, T, [complex], and decreased by increasing ionic strength over the range studied.     

A comparative study of quinolinium dichromate oxidation with hydrophobic dependence amino acids. A kinetic and mechanistic approach

A detailed study of kinetics is required to predict the susceptibility of amino acid residues towards metal-catalyzed oxidation. The effect of quinolinium dichromate on the oxidation of a set of amino acid residues with different hydrophobicity in HClO₄ medium at 25 °C has been fairly studied. The kinetics of the reaction was followed spectrophotometrically at λ_max = 440 nm. The reaction has unit dependence on each of the substrates, quinolinum dichromate and acid concentrations. The effect of dielectric constant of the medium on the rate was studied. The induced polymerization of acrylonitrile was observed. The oxidation products were isolated and characterized. Dependence of reaction rate on temperature has been studied and activation parameters were computed. A mechanism consistent with the observed results has been proposed. Of the four amino acid residues, proline is oxidized at a faster rate than all other amino acids. This may be due to the hydrophobic induced oxidation. Therefore, the overall order of amino acid sensitivity to oxidation was found to be Pro > Thr > Ser > Lys.